Substance P and Somatostatin are two of several neuropeptides that have been identified within the mammalian vagus nerve. Evidence suggests that within this nerve the two peptides originate exclusively in bipolar cell bodies located in vagal sensory ganglia from where they are transported towards the central nervous system (medulla oblongata) and peripherally towards the thorax and abdomen. This project will study the factors regulating peripheral transport of these neuropeptides within the vagus nerve of the rat and guinea pig. The experiments will test the hypothesis that transport is regulated by three factors: 1) the frequency or intensity of neural impulses reaching the sensory ganglia; 2) the effects of hormones acting directly on sensory cell bodies; and 3) alterations of sensory transmission within the medulla oblongata. Experiments will measure the accumulation of substance P and somatostatin proximal to ligature or colchicine interruption of axoplasmic transport. This will be done in conjunction with electrical stimulation of the vagus, hormone infusion, or following alterations in neurotransmitters or neuromodulators within the medulla oblongata. The time course of synthesis and presence of other immunoreactive forms of these peptides will be evaluated following the injection of radiolabelled amino acid precursors into the nodose ganglion. As an in vitro correlate of this work, I will develop dissociated cell cultures of nodose ganglion cells and evaluate factors effecting substance P and somatostatin synthesis and release. Finally, as a preliminary study of the peripheral effects of sensory vagus substance P and somatostatin, I will measure the effects of their depletion from the sensory vagus nerve on the stimulated secretion of insulin and somatostatin into the hepatic portal vein.